A Phase 2, Open Label, Single Arm, Clinical Trial of Neoadjuvant Nivolumab and Relatlimab in Stage II To IV (M0) Resectable Cutaneous Squamous Cell Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Nivolumab 240 mg / Relatlimab 80 mg in a fixed dose combination
- Conditions
- Cutaneous Squamous Cell Carcinoma
- Sponsor
- Melanoma Institute Australia
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Pathological complete response rate
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
The goal of this study is to test neoadjuvant therapy with the dual inhibition of Programmed cell death protein 1 (PD-1) and lymphocyte activation gene 3 (LAG-3) immune checkpoint pathways in a cohort of treatment-naïve, resectable stage II to IV cutaneous squamous cell carcinoma on the pathological response rate (pCR) and recurrence-free survival.
Detailed Description
This is a phase 2, open label, single cohort, single centre, clinical trial of neoadjuvant immunotherapy with dual inhibition of PD-1 and LAG-3 immune checkpoint pathways. The hypothesis is that neoadjuvant therapy produces a higher pathological response rate (pCR) and a longer recurrence-free survival in a cohort of treatment-naïve patients with resectable stage II to IV (M0) cutaneous squamous cell carcinoma compared to neoadjuvant cemiplimab monotherapy in Checkmate 358 (n=123, NCT02488759, historical control).
Investigators
Eligibility Criteria
Inclusion Criteria
- •≥ 18 years of age
- •Written informed consent
- •Histologically confirmed, resectable stage II to IV cutaneous squamous cell carcinoma defined as:
- •Non-head and neck cuSCC:
- •stage II (T2, N0, M0)
- •stage III (T3, N0, M0; or T1-3, N1, M0)
- •stage IV (T1-3, N2 or N3, M0; or T4a or T4b, any N, M0)
- •Cutaneous head and neck CC:
- •stage II (T2, N0, M0)
- •stage III (T3, N0, M0)
Exclusion Criteria
- •Clinical or radiographic evidence of distant metastasis
- •SCC of the eyelid, vulva, penis and perianus
- •Any contraindication to the administration of nivolumab and / or relatlimab
- •Prior anti-PD-1, CTLA-4 (Cytotoxic T-lymphocyte associated protein 4), PDL-1 (Programmed death-ligand 1) or LAG 3 (Lymphocyte-Activation Gene 3) antibody exposure, or an agent directed to another stimulatory or co-inhibitory T-cell receptor for any disease or any chemotherapy or experimental local or systemic drug treatment
- •Active autoimmune disease or a requirement for chronic steroid therapy other than hormone replacement therapy
- •The following are permitted:
- •Type I diabetes mellitus on stable insulin therapy
- •Residual autoimmune hypothyroidism on stable hormone replacement
- •Resolved childhood asthma or atopy
- •Psoriasis not requiring systemic treatment
Arms & Interventions
Neoadjuvant Treatment
Nivolumab and relatlimab will be administered in a fixed dose combination (FDC). The dose and dosing regimen for this study is nivolumab 480 mg and relatlimab 160 mg - 2 vials per infusion. All patients are scheduled to receive two doses of nivolumab and relatlimab FDC prior to surgery on days 1 and 29. Patients without a complete pathological response to neoadjuvant therapy may receive standard of care radiotherapy per multidisciplinary team meeting discussion.
Intervention: Nivolumab 240 mg / Relatlimab 80 mg in a fixed dose combination
Outcomes
Primary Outcomes
Pathological complete response rate
Time Frame: Week 6
Proportion of patients with a pathological complete response, as determined on the week 6 surgical specimen using the guidelines published by the International Neoadjuvant Melanoma Consortium: Complete pathological response (pCR) = 0% viable tumour cells in the surgical specimen
Secondary Outcomes
- Disease progression rate(Week 6)
- Toxicity and tolerability of neoadjuvant immunotherapy and surgery(Week 24)
- Objective response rate to neoadjuvant therapy(Week 6)
- Recurrence-free survival(10 years)
- Patient reported quality of life (QLQ-C30)(1 year)
- Patient reported quality of life (EQ-5L-5D)(1 year)
- Study treatment completion rate and the causes of any missed treatments(Week 8)
- Pathological near pathological response (near pCR), partial response (pPR) and pathological non-response (pNR) rate(Week 6)
- Metabolic response rate to neoadjuvant immunotherapy(Week 6)
- Event-free survival rate(10 years)
- Overall survival(10 years)
- De-escalation of adjuvant radiotherapy.(Week 8)